Diisopropylethylamine → tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(methylsulfonyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

HRID 1454198Notes

Reaction equation

HRID 1454198 reaction equation
C[C:2]1[C:10]([C:11](=[O:13])[CH3:12])=[CH:9][C:8]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:51][O:52][C:53]1[CH:54]=[C:55]([CH:79]=[CH:80][CH:81]=1)[CH2:56][N:57]([CH2:65][C@@H:66]([OH:78])[C@@H:67]([NH2:77])[CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:62])[CH3:61]>CN(C=O)C.C(OCC)(=O)C>[CH3:51][O:52][C:53]1[CH:54]=[C:55]([CH:79]=[CH:80][CH:81]=1)[CH2:56][N:57]([CH2:65][C@@H:66]([OH:78])[C@@H:67]([NH:77][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([S:14]([CH3:17])(=[O:15])=[O:16])[CH:9]=[C:10]([C:11](=[O:13])[CH3:12])[CH:2]=1)[CH2:68][C:69]1[CH:70]=[C:71]([F:76])[CH:72]=[C:73]([F:75])[CH:74]=1)[C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:61])[CH3:62]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamateHCID 68830431Methyl 3-acetyl-5-(methylsulfonyl)benzoic acid

Product 1

HCID 57529302tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(methylsulfonyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamateYield 49.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of methyl 3-acetyl-5-(methylsulfonyl)benzoic acid (52 mg, 0.215 mmol), HATU (98 mg, 0.258 mmol) and Hunig's base (111.1 mg, 0.15 mL, 0.86 mmol) in DMF (1.0 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate (94 mg, 0.215 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with H2O 3 times and concentrated under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (70 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.48 (9H, s), 2.70 (3H, s), 2.87-2.90 (1H, m), 3.11-3.15 (2H, m), 3.20 (3H, s), 3.37 (1H, m), 3.76 (3H, s), 3.79-3.80 (1H, m), 3.99 (1H, m), 4.33-4.39 (1H, m), 4.43-4.47 (1H, m), 6.73 (1H, m), 6.80-6.83 (3H, m), 6.91 (2H, m), 7.21-7.25 (1H, m), 8.45 (1H, m), 8.54 (1H, m), 8.61 (1H, m). HPLC retention time: 2.022 min (method B). MS (ESI) (M+H)+ 661.14.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. washwashed with H2O 3 times
  3. concentrationconcentrated under vacuum
  4. customThe crude mixture was purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-b0bdea22bba44a7787550390eebcddc4
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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